Estrogen receptor beta (ER beta), first reported in 1996, is the second estrogen receptor cloned. Like the original estrogen receptor (ER alpha), ER beta has the ability to act as a transcription factor by binding estrogen. The amino-terminal domain of ER beta differs considerably from that of ER alpha, while the DNA binding domain is highly homologous, and the hormone binding and carboxyl-terminal domains are partially homologous, to ER alpha.
While ER beta, like ER alpha, binds hormone and modulates changes in transcription, a fundamental question has been whether ER beta possesses additional function(s). ER beta has been postulated to play a role in the cardiovascular system and may be involved in the vascular protective effects of estrogen (Iafrati et al., Nat. Med. 3:545-8, 1997). An estrogen receptor alpha knock-out mouse was still protected against vascular injury upon estrogen administration. This implied another way for estrogen to exert its protective effects and led to the discovery of ER beta in blood vessels. ER beta was discovered in the rat prostate, originally, and was then found to be expressed in blood vessels, including the blood vessels of the ER knock-out mouse. Furthermore, if a blood vessel of a male rat is injured, regrowth of endothelial and smooth muscle cells occurs as that injury repairs itself, accompanied by a dramatic increase in ER beta expression at the leading edge of cells as they grow back. There is no change in the expression of ER alpha in this setting (Lindner et al., Circ. Res. 83:224-9, 1998).